Figure 1.

AZD5634 is a potent and durable inhibitor of ENaC in human, sheep, and rats. A: effective concentration (EC) curves for AZD5634 (EC₅₀ 3.8 nM, n = 6 replicates), benzamil (EC₅₀ 21.9 nM, n = 13 replicates), and amiloride (EC₅₀ 0.454 µM, n = 2 replicates) in the Ussing chamber assay on normal human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures from healthy donors. All traces were normalized to 100% for the final dose of 10 µM benzamil following the cumulative concentration of the tested drugs. B: EC curves for AZD5634 (EC₅₀ 5.5 nM, n = 5 replicates) in the Ussing chamber assay on ALI bronchial epithelial cells from normal sheep. C: duration of effect by AZD5634 on airway surface liquid (ASL) in ALIs from human bronchial epithelial (HBE) cells determined by gravimetric method indicates a duration of fluid-retaining effect >24 h by concentrations of 0.1 µM and above (n = 6 replicates). Means ± SE. ENaC, epithelial sodium channel.